We have identified side population (SP) cells in the adult mouse thyroid. SP cells are characterized by their ability to efflux the vital dye Hoechst 33342 when analyzed by flow cytometry, due to expression of the ATP binding cassette (ABC)-dependent transporter ABCG2, and are highly enriched for stem/progenitor cell activity. Thyroid SP cells highly express ABCG2 and the stem cell marker genes encoding nucleostemin and Oct4, whereas the expression of genes encoding the thyroid differentiation markers such as thyroid peroxidase, thyroglobulin, and TSH receptor, and two transcription factors, T/EBP and PAX8, critical for thyroid specific gene expression, are low in the SP fraction of cells as examined by RT- and real-time PCR. These results suggest that adult thyroid may contain stem/progenitor cells. Our current focus is to identify another cell surface marker that can be used in conjunction with SP fraction to further enrich thyroid stem/progenitor-like cells. As one of proof that they are the genuine stem/progenitor cells of thyroid, we culture these cells in culture dish and/or collagen gel three dimensional system, to induce thyroid-specific gene expression and/or thyroid cell-like morphology.